Genomics in Neurological Disorders

Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center （i.e., the brain） in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be dis- cussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer＇s disease and autism spectrum disorder.     

nhe regulation and deregulation of Wnt signaling by PARK genes in health and disease

Wingless/Int （Wnt） signaling pathways are signal transduction mechanisms that have been widely studied In the field of embryogen- esis. Recent work has established a critical role for these pathways in brain development, especially of midbrain dopaminergic neu- rones, However, the fundamental importance of Wnt signaling for the normal function of mature neurones in the adult central nervous system has also lately been demonstrated by an increasing number of studies. Parkinson＇s disease （PD） is the second most prevalent neurodegenerative disease worldwide and is currently incurable. This debilitating disease is characterized by the progres- sive loss of a subset of midbrain dopaminergic neurones in the substontla nigm leadingto typical extrapyramidal motor symptoms. The aetiology of PD is poorly understood but work performed over the Last two decades has identified a growing number of genetic defects that underlie this condition. Herewe review a growing body of data connecting genes implicated in PD--most notablythe PARKgenes-- with Wnt signaling. These observations provide clues to the normal function of these proteins in healthy neurones and suggest that deregulated Wnt signaling might be a frequent pathomechanlsm leading to PD. These observations have implications for the patho- genesis and treatment of neurodegenerative diseases in general.     

氢气生物医学研究进展

氢气以其安全、有效、渗透性强、代谢产物只有水等特点,逐渐进入医学研究者和临床工作者的视野,并在近年来快速发展。大量研究证明,氢气对于包括肿瘤、炎症损伤、代谢疾病、神经性疾病等百余种疾病具有潜在的治疗作用。2020年新型冠状病毒肺炎（新冠肺炎）疫情全球大流行期间,氢气在新冠肺炎辅助治疗中也崭露头角。对氢气在生物医学的动物学、细胞学和临床研究领域的研究进展进行了总结,并主要综述了氢气在代谢性疾病、神经退行性疾病、急救和创伤医学以及肿瘤领域的研究进展,以期为氢气在生物医学领域的应用研究提供参考。     

与人类疾病相关的淀粉样短肽

有些天然蛋白质可通过错误折叠形成淀粉样纤维,并进一步沉积导致淀粉样病变,被认为是许多重大人类疾病的病理基础。因此,阐明天然蛋白质错误折叠、聚集形成淀粉样纤维的分子机制,是预防、诊断和治疗相关疾病的关键。研究者们从天然蛋白质中鉴定出许多能够形成淀粉样纤维的关键短肽片段,即淀粉样短肽,对它们形成淀粉样纤维的能力及其在完整蛋白质聚集过程中的决定性作用进行深入研究。本文对近年来人类疾病相关淀粉样短肽的研究展开综述。首先,介绍鉴定淀粉样短肽的标准及其相应的研究方法和技术手段;并回顾近年来与一些重大人类疾病相关的淀粉样短肽,尤其是与神经退行性疾病相关淀粉样短肽的进展情况,对淀粉样短肽中出现频率较高的氨基酸残基及其可能的自组装原理进行总结分析;最后,展望这些淀粉样短肽作为靶点在相关疾病诊断和治疗方面的意义,并初步探讨它们作为新型生物材料在生物医学工程领域的应用前景。本文一方面为阐明天然蛋白质形成淀粉样沉淀的分子机制提供参考,另一方面也为相关疾病的治疗提供思路,同时也为新型生物材料的开发提出潜在的可能性。     

综述与专论: 星形胶质细胞对神经退行性疾病影响的研究进展

神经退行性疾病是常见且难以治愈的疾病,给患者的生活带来了极大的不便。星形胶质细胞在神经退行性疾病中发挥重要作用。在神经退行性疾病患者神经系统中,受损的神经胶质细胞对周围的神经元可以产生毒性作用,造成神经元功能障碍,从而死亡。同时,受疾病影响产生的一些反应性星形胶质细胞可以保护神经元,清除神经元周围的有害物质,暂缓疾病的恶化。本综述将讨论星形胶质细胞在部分常见神经退行性疾病中发挥的作用,包括肌萎缩侧索硬化（amyotrophic lateral sclerosis,ALS）、阿尔茨海默病（Alzheimer’s disease,AD）和帕金森病（Parkinson’s disease,PD）。同时总结了星形胶质细胞对这些疾病发挥的共同作用,旨在进一步促进神经退行性疾病的研究进展。     

腰椎间融合器植入术治疗腰椎退行性疾病的临床疗效

目的:观察腰椎融合术结合腰椎间融合器植入对腰椎退行性疾病的治疗效果及对预后评估。方法:选择我院2013年1月至2014年1月收治的54例腰椎退行性疾病患者为研究对象,随机将其分为两组,对照组患者行单纯椎间植骨融合术,实验组患者给予腰椎融合术结合腰椎间融合器植入治疗,对两组患者的手术时间、手术失血量、住院天数、融合率及并发症情况进行观察,同时对术前、术后三个月均应用VAS评分、ODI评分评估患者恢复情况。结果:实验组融合率明显高于对照组,但实验组手术时间较对照组长,差异具有统计学意义(P0.05);两组术中出血量及住院天数无统计学意义(P0.05);与术前比较,两组患者VAS评分、ODI评分均明显降低,差异具有统计学意义(P0.05);与对照组比较,实验组术后VAS评分和ODI评分降低更明显,差异具有统计学意义(P0.05);疗效与并发症比较,实验组优于对照组(P0.05)。结论:腰椎融合术结合腰椎间融合器植入治疗腰椎退行性疾病临床疗效显著且安全性高,对患者预后较好。     

Chemical genetics and drug screening in Drosophila cancer models

Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety.It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later.In this regard,it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays.Drosophila melanogaster has emerged as a potential whole animal model for drug screening.Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer.A recent review provides a comprehensive summary of drug screening in Drosophila,but with an emphasis on neurodegenerative disorders.Here,we review Drosophila screens in the literature aimed at cancer therapeutics.     

一个强大的蛋白质

肌萎缩侧索硬化（ALS）是一种致命性的神经退行性疾病,主要特征是运动神经元功能的急剧丧失。从研究者第一次命名这个疾病开始,引起ALS或者因为患病累积的蛋白仍然是一个谜。     

5-脂氧合酶在中枢神经系统的作用

5－脂氧合酶（5LO）是机体催化花生四烯酸生成生物活性分子白三烯的关键酶,中枢神经系统神经元有5LO的显著表达,海马和小脑表达水平最高。5LO在体外神经元发育、老化及多种脑损伤过程中表达增高。5LO可能通过酶和非酶功能在中枢神经系统的生理和病理机制中发挥作用。糖皮质激素、褪黑素等参与5LO的转录调节。